Generic placeholder image

Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Review Article

Combinatory Approaches Targeting Cognitive Impairments and Memory Enhancement: A Review

Author(s): Varun Santosh Gupta and Pravin Popatrao Kale*

Volume 24, Issue 1, 2023

Published on: 25 October, 2022

Page: [55 - 70] Pages: 16

DOI: 10.2174/1389450123666220928152743

Price: $65

Abstract

The objective of this paper is to look at how natural medicines can improve cognition and memory when used with sildenafil, a popular erectile dysfunction medicine that also has nootropic properties. Newer treatment strategies to treat the early stages of these diseases need to be developed. Multiple factors lead to complex pathophysiological conditions, which are responsible for various long-term complications. In this review, a combination of treatments targeting these pathologies is discussed. These combinations may help manage early and later phases of cognitive impairments. The purpose of this article is to discuss a link between these pathologies and a combinational approach with the objective of considering newer therapeutic strategies in the treatment of cognitive impairments. The natural drugs and their ingredients play a major role in the management of disease progression. Additionally, their combination with sildenafil allows for more efficacy and better response. Studies showing the effectiveness of natural drugs and sildenafil are mentioned, and how these combinations could be beneficial for the treatment of cognitive impairments and amnesia are summarised. Furthermore, preclinical and clinical trials are required to explore the medicinal potential of these drug combinations.

Keywords: memory, natural nootropics, anti-amnestic, neurodegenerative diseases, cognitive impairments, dementia

Graphical Abstract

[1]
Du X, Wang X, Geng M. Alzheimer’s disease hypothesis and related therapies. Transl Neurodegener 2018; 7(1): 2.
[http://dx.doi.org/10.1186/s40035-018-0107-y] [PMID: 29423193]
[2]
Rajan KB, Weuve J, Barnes LL, McAninch EA, Wilson RS, Evans DA. Population estimate of people with clinical Alzheimer’s disease and mild cognitive impairment in the United States (2020–2060). Alzheimers Dement 2021; 17(12): 1966-75.
[http://dx.doi.org/10.1002/alz.12362] [PMID: 34043283]
[3]
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease. Neurology 1984; 34(7): 939-44.
[4]
Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 2011; 1(1): a006189.
[http://dx.doi.org/10.1101/cshperspect.a006189] [PMID: 22229116]
[5]
Jahn H. Memory loss in Alzheimer’s disease. Dialogues Clin Neurosci 2013; 15(4): 445-54.
[http://dx.doi.org/10.31887/DCNS.2013.15.4/hjahn] [PMID: 24459411]
[6]
Roy E. Cognitive impairment. In: Gellman MD, Turner JR, Eds. Encyclopedia of Behavioral Medicine. 449-51.
[7]
Argyrousi EK, Heckman PRA, Prickaerts J. Role of cyclic nucleotides and their downstream signaling cascades in memory function: Being at the right time at the right spot. Neurosci Biobehav Rev 2020; 113: 12-38.
[http://dx.doi.org/10.1016/j.neubiorev.2020.02.004] [PMID: 32044374]
[8]
Rosa E, Fahnestock M. CREB expression mediates amyloid β-induced basal BDNF downregulation. Neurobiol Aging 2015; 36(8): 2406-13.
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.04.014] [PMID: 26025137]
[9]
Hock C, Heese K, Hulette C, Rosenberg C, Otten U. Region-specific neurotrophin imbalances in Alzheimer disease: Decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol 2000; 57(6): 846-51.
[http://dx.doi.org/10.1001/archneur.57.6.846] [PMID: 10867782]
[10]
Chao MV. Neurotrophins and their receptors: A convergence point for many signalling pathways. Nat Rev Neurosci 2003; 4(4): 299-309.
[http://dx.doi.org/10.1038/nrn1078] [PMID: 12671646]
[11]
Huang EJ, Reichardt LF. Neurotrophins: Roles in neuronal development and function. Annu Rev Neurosci 2001; 24(1): 677-736.
[http://dx.doi.org/10.1146/annurev.neuro.24.1.677] [PMID: 11520916]
[12]
Budni J, Bellettini-Santos T, Mina F, et al. The involvement of BDNF, NGF and GDNF in aging and Alzheimer’s disease. Aging Dis 2015; 6(5): 331-41.
[http://dx.doi.org/10.14336/AD.2015.0825] [PMID: 26425388]
[13]
Impey S, Smith DM, Obrietan K, Donahue R, Wade C, Storm DR. Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning. Nat Neurosci 1998; 1(7): 595-601.
[http://dx.doi.org/10.1038/2830] [PMID: 10196567]
[14]
Barco A, Pittenger C, Kandel ER. CREB, memory enhancement and the treatment of memory disorders: Promises, pitfalls and prospects. Expert Opin Ther Targets 2003; 7(1): 101-14.
[http://dx.doi.org/10.1517/14728222.7.1.101] [PMID: 12556206]
[15]
Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 1994; 79(1): 59-68.
[http://dx.doi.org/10.1016/0092-8674(94)90400-6] [PMID: 7923378]
[16]
Cohen S, Greenberg ME. Communication between the synapse and the nucleus in neuronal development, plasticity, and disease. Annu Rev Cell Dev Biol 2008; 24(1): 183-209.
[http://dx.doi.org/10.1146/annurev.cellbio.24.110707.175235] [PMID: 18616423]
[17]
Won J, Silva AJ. Molecular and cellular mechanisms of memory allocation in neuronetworks. Neurobiol Learn Mem 2008; 89(3): 285-92.
[http://dx.doi.org/10.1016/j.nlm.2007.08.017] [PMID: 17962049]
[18]
Walton MR, Dragunow M. Is CREB a key to neuronal survival? Trends Neurosci 2000; 23(2): 48-53.
[http://dx.doi.org/10.1016/S0166-2236(99)01500-3] [PMID: 10652539]
[19]
Sanders O. Sildenafil for the treatment of Alzheimer’s disease: A systematic review. J Alzheimers Dis Rep 2020; 4(1): 91-106.
[http://dx.doi.org/10.3233/ADR-200166] [PMID: 32467879]
[20]
Servello A, Leccese V, Ettorre E. Natural products for neurocognitive disorders. Exon Publications 2020; pp. 205-20.
[21]
Sharifi-Rad M, Lankatillake C, Dias DA, et al. Impact of natural compounds on neurodegenerative disorders: From preclinical to pharmacotherapeutics. J Clin Med 2020; 9(4): 1061.
[http://dx.doi.org/10.3390/jcm9041061] [PMID: 32276438]
[22]
Froestl W, Muhs A, Pfeifer A. Cognitive enhancers (nootropics). Part 1: Drugs interacting with receptors. J Alzheimers Dis 2012; 32(4): 793-887.
[http://dx.doi.org/10.3233/JAD-2012-121186] [PMID: 22886028]
[23]
Parle M, Dhingra D, Kulkarni SK. Improvement of mouse memory by Myristica fragrans seeds. J Med Food 2004; 7(2): 157-61.
[http://dx.doi.org/10.1089/1096620041224193] [PMID: 15298762]
[24]
Majumdar S, Gupta S, Prajapati SK, Krishnamurthy S. Neuro-nutraceutical potential of Asparagus racemosus: A review. Neurochem Int 2021; 145: 105013.
[http://dx.doi.org/10.1016/j.neuint.2021.105013] [PMID: 33689806]
[25]
Birla H, Keswani C, Rai SN, et al. Neuroprotective effects of Withania somnifera in BPA induced-cognitive dysfunction and oxidative stress in mice. Behav Brain Funct 2019; 15(1): 9.
[http://dx.doi.org/10.1186/s12993-019-0160-4] [PMID: 31064381]
[26]
Yin JCP, Del Vecchio M, Zhou H, Tully T. CREB as a memory modulator: Induced expression of a dCREB2 activator isoform enhances long-term memory in drosophila. Cell 1995; 81(1): 107-15.
[http://dx.doi.org/10.1016/0092-8674(95)90375-5] [PMID: 7720066]
[27]
Abel T, Nguyen PV, Barad M, Deuel TAS, Kandel ER, Bourtchouladze R. Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell 1997; 88(5): 615-26.
[http://dx.doi.org/10.1016/S0092-8674(00)81904-2] [PMID: 9054501]
[28]
Lu YF, Kandel ER, Hawkins RD. Nitric oxide signaling contributes to late-phase LTP and CREB phosphorylation in the hippocampus. J Neurosci 1999; 19(23): 10250-61.
[http://dx.doi.org/10.1523/JNEUROSCI.19-23-10250.1999] [PMID: 10575022]
[29]
Müller U, Bicker G. Calcium-activated release of nitric oxide and cellular distribution of nitric oxide-synthesizing neurons in the nervous system of the locust. J Neurosci 1994; 14(12): 7521-8.
[http://dx.doi.org/10.1523/JNEUROSCI.14-12-07521.1994] [PMID: 7527844]
[30]
Bicker G. Sources and targets of nitric oxide signalling in insect nervous systems. Cell Tissue Res 2001; 303(2): 137-46.
[http://dx.doi.org/10.1007/s004410000321] [PMID: 11291761]
[31]
Matsumoto Y, Unoki S, Aonuma H, Mizunami M. Critical role of nitric oxide-cGMP cascade in the formation of cAMP-dependent long-term memory. Learn Mem 2006; 13(1): 35-44.
[http://dx.doi.org/10.1101/lm.130506] [PMID: 16452652]
[32]
Scott BR. Cyclic AMP response element-binding protein (CREB) phosphorylation: A mechanistic marker in the development of memory enhancing Alzheimer’s disease therapeutics. Biochem Pharmacol 2012; 83(6): 705-14.
[http://dx.doi.org/10.1016/j.bcp.2011.11.009] [PMID: 22119240]
[33]
Ueda Y, Hirai S, Osada S, Suzuki A, Mizuno K, Ohno S. Protein kinase C activates the MEK-ERK pathway in a manner independent of Ras and dependent on Raf. J Biol Chem 1996; 271(38): 23512-9.
[http://dx.doi.org/10.1074/jbc.271.38.23512] [PMID: 8798560]
[34]
Mizunami M, Nemoto Y, Terao K, Hamanaka Y, Matsumoto Y. Roles of calcium/calmodulin-dependent kinase II in long-term memory formation in crickets. PLoS One 2014; 9(9): e107442.
[http://dx.doi.org/10.1371/journal.pone.0107442] [PMID: 25215889]
[35]
Bach ME, Barad M, Son H, et al. Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc Natl Acad Sci 1999; 96(9): 5280-5.
[http://dx.doi.org/10.1073/pnas.96.9.5280] [PMID: 10220457]
[36]
Nguyen PV, Kandel ER. Brief theta-burst stimulation induces a transcription-dependent late phase of LTP requiring cAMP in area CA1 of the mouse hippocampus. Learn Mem 1997; 4(2): 230-43.
[http://dx.doi.org/10.1101/lm.4.2.230] [PMID: 10456066]
[37]
Frey U, Huang YY, Kandel ER. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science 1993; 260(5114): 1661-4.
[http://dx.doi.org/10.1126/science.8389057] [PMID: 8389057]
[38]
Impey S, Mark M, Villacres EC, Poser S, Chavkin C, Storm DR. Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus. Neuron 1996; 16(5): 973-82.
[http://dx.doi.org/10.1016/S0896-6273(00)80120-8] [PMID: 8630255]
[39]
Matsushita M, Tomizawa K, Moriwaki A, Li Sheng-Tian, Terada H, Matsui H. A high-efficiency protein transduction system demonstrating the role of pka in long-lasting long-term potentiation. J Neurosci Res 2001; 21(16): 6000-7.
[40]
Hu H, Real E, Takamiya K, et al. Emotion enhances learning via norepinephrine regulation of AMPA-receptor trafficking. Cell 2007; 131(1): 160-73.
[http://dx.doi.org/10.1016/j.cell.2007.09.017] [PMID: 17923095]
[41]
Derkach VA, Oh MC, Guire ES, Soderling TR. Regulatory mechanisms of AMPA receptors in synaptic plasticity. Nat Rev Neurosci 2007; 8(2): 101-13.
[http://dx.doi.org/10.1038/nrn2055] [PMID: 17237803]
[42]
Nguyen PV, Abel T, Kandel ER. Requirement of a critical period of transcription for induction of a late phase of LTP. Science 1994; 265(5175): 1104-7.
[http://dx.doi.org/10.1126/science.8066450] [PMID: 8066450]
[43]
Esteban JA, Shi SH, Wilson C, Nuriya M, Huganir RL, Malinow R. PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nat Neurosci 2003; 6(2): 136-43.
[http://dx.doi.org/10.1038/nn997] [PMID: 12536214]
[44]
Matsuoka I, Giuili G, Poyard M, et al. Localization of adenylyl and guanylyl cyclase in rat brain by in situ hybridization: Comparison with calmodulin mRNA distribution. J Neurosci 1992; 12(9): 3350-60.
[http://dx.doi.org/10.1523/JNEUROSCI.12-09-03350.1992] [PMID: 1356144]
[45]
Schulz S, Yuen PST, Garbers DL. The expanding family of guanylyl cyclases. Trends Pharmacol Sci 1991; 12(3): 116-20.
[http://dx.doi.org/10.1016/0165-6147(91)90519-X] [PMID: 1675819]
[46]
Sanchez JJ, Abreu P, Gonzalez MC. Sodium nitroprusside stimulates l-DOPA release from striatal tissue through nitric oxide and cGMP. Eur J Pharmacol 2002; 438(1-2): 79-83.
[http://dx.doi.org/10.1016/S0014-2999(02)01286-4] [PMID: 11906714]
[47]
Arancio O, Kiebler M, Lee CJ, et al. Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. Cell 1996; 87(6): 1025-35.
[http://dx.doi.org/10.1016/S0092-8674(00)81797-3] [PMID: 8978607]
[48]
Stone JR, Marletta MA. Spectral and kinetic studies on the activation of soluble guanylate cyclase by nitric oxide. Biochemistry 1996; 35(4): 1093-9.
[http://dx.doi.org/10.1021/bi9519718] [PMID: 8573563]
[49]
Ignarro LJ, Wood KS, Wolin MS. Activation of purified soluble guanylate cyclase by protoporphyrin IX. Proc Natl Acad Sci 1982; 79(9): 2870-3.
[http://dx.doi.org/10.1073/pnas.79.9.2870] [PMID: 6123998]
[50]
Lu YF, Hawkins RD. Ryanodine receptors contribute to cGMP-induced late-phase LTP and CREB phosphorylation in the hippocampus. J Neurophysiol 2002; 88(3): 1270-8.
[http://dx.doi.org/10.1152/jn.2002.88.3.1270] [PMID: 12205148]
[51]
Prickaerts J, de Vente J, Honig W, Steinbusch HWM, Blokland A. cGMP, but not cAMP, in rat hippocampus is involved in early stages of object memory consolidation. Eur J Pharmacol 2002; 436(1-2): 83-7.
[http://dx.doi.org/10.1016/S0014-2999(01)01614-4] [PMID: 11834250]
[52]
Zhang M, Wang H. Mice overexpressing type 1 adenylyl cyclase show enhanced spatial memory flexibility in the absence of intact synaptic long-term depression. Learn Mem 2013; 20(7): 352-7.
[PMID: 23772089]
[53]
Banday AA, Lokhandwala MF. Oxidative stress impairs cgmp-dependent protein kinase activation and vasodilator-stimulated phosphoprotein serine-phosphorylation. Clin Exp Hypertens 2019; 41: 5-13.
[54]
Stephens RS, Rentsendorj O, Servinsky LE, Moldobaeva A, Damico R, Pearse DB. cGMP increases antioxidant function and attenuates oxidant cell death in mouse lung microvascular endothelial cells by a protein kinase G-dependent mechanism. Am J Physiol Lung Cell Mol Physiol 2010; 299(3): L323-33.
[http://dx.doi.org/10.1152/ajplung.00442.2009] [PMID: 20453163]
[55]
Floyd R, Hensley K. Oxidative stress in brain agingImplications for therapeutics of neurodegenerative diseases. Neurobiol Aging 2002; 23(5): 795-807.
[http://dx.doi.org/10.1016/S0197-4580(02)00019-2] [PMID: 12392783]
[56]
Sohal RS, Orr WC. The redox stress hypothesis of aging. Free Radic Biol Med 2012; 52(3): 539-55.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.445] [PMID: 22080087]
[57]
Butterfield DA, Perluigi M, Sultana R. Oxidative stress in Alzheimer’s disease brain: New insights from redox proteomics. Eur J Pharmacol 2006; 545(1): 39-50.
[http://dx.doi.org/10.1016/j.ejphar.2006.06.026] [PMID: 16860790]
[58]
Smith BP, Babos M. Sildenafil Treasure Island, FL,: StatPearls Publishing: Treasure Island. 2021.
[59]
Singh N, Parle M. Sildenafil improves acquisition and retention of memory in mice. Indian J Physiol Pharmacol 2003; 47(3): 318-24.
[PMID: 14723318]
[60]
Steen E, Terry BM, Rivera EJ, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease-is this type 3 diabetes? J Alzheimers Dis 2005; 7(1): 63-80.
[http://dx.doi.org/10.3233/JAD-2005-7107] [PMID: 15750215]
[61]
Devan B, Sierramercado D Jr, Jimenez M, et al. Phosphodiesterase inhibition by sildenafil citrate attenuates the learning impairment induced by blockade of cholinergic muscarinic receptors in rats. Pharmacol Biochem Behav 2004; 79(4): 691-9.
[http://dx.doi.org/10.1016/j.pbb.2004.09.019] [PMID: 15582676]
[62]
Puzzo D, Loreto C, Giunta S, et al. Effect of phosphodiesterase-5 inhibition on apoptosis and beta amyloid load in aged mice. Neurobiol Aging 2014; 35(3): 520-31.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.09.002] [PMID: 24112792]
[63]
Fang J, Zhang P, Zhou Y, et al. Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer’s disease. Nature Aging 2021; 1(12): 1175-88.
[http://dx.doi.org/10.1038/s43587-021-00138-z] [PMID: 35572351]
[64]
Hervé R, Schmitz T, Evain-Brion D, Cabrol D, Leroy MJ, Méhats C. The PDE4 inhibitor rolipram prevents NF-kappaB binding activity and proinflammatory cytokine release in human chorionic cells. J Immunol 2008; 181(3): 2196-202.
[http://dx.doi.org/10.4049/jimmunol.181.3.2196] [PMID: 18641359]
[65]
Chen Y, Zhuang S, Cassenaer S, et al. Synergism between calcium and cyclic GMP in cyclic AMP response element-dependent transcriptional regulation requires cooperation between CREB and C/EBP-beta. Mol Cell Biol 2003; 23(12): 4066-82.
[http://dx.doi.org/10.1128/MCB.23.12.4066-4082.2003] [PMID: 12773552]
[66]
Ciani E, Guidi S, Bartesaghi R, Contestabile A. Nitric oxide regulates cGMP-dependent cAMP-responsive element binding protein phosphorylation and Bcl-2 expression in cerebellar neurons: Implication for a survival role of nitric oxide. J Neurochem 2002; 82(5): 1282-9.
[http://dx.doi.org/10.1046/j.1471-4159.2002.01080.x] [PMID: 12358775]
[67]
Domek-Łopacińska KU, Strosznajder JB. Cyclic GMP and nitric oxide synthase in aging and Alzheimer’s disease. Mol Neurobiol 2010; 41(2-3): 129-37.
[http://dx.doi.org/10.1007/s12035-010-8104-x] [PMID: 20213343]
[68]
Banerjee J, Bruckbauer A, Thorpe T, Zemel MB. Biphasic effect of sildenafil on energy sensing is mediated by phosphodiesterases 2 and 3 in adipocytes and hepatocytes. Int J Mol Sci 2019; 20(12): 2992.
[http://dx.doi.org/10.3390/ijms20122992] [PMID: 31248114]
[69]
Orejana L, Barros-Miñones L, Aguirre N, Puerta E. Implication of JNK pathway on tau pathology and cognitive decline in a senescence-accelerated mouse model. Exp Gerontol 2013; 48(6): 565-71.
[http://dx.doi.org/10.1016/j.exger.2013.03.001] [PMID: 23501261]
[70]
Cuadrado-Tejedor M, Hervias I, Ricobaraza A, et al. Sildenafil restores cognitive function without affecting β-amyloid burden in a mouse model of Alzheimer’s disease. Br J Pharmacol 2011; 164(8): 2029-41.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01517.x] [PMID: 21627640]
[71]
Moreira SG Jr, Brannigan RE, Spitz A, Orejuela FJ, Lipshultz LI, Kim ED. Side-effect profile of sildenafil citrate (Viagra) in clinical practice. Urology 2000; 56(3): 474-6.
[http://dx.doi.org/10.1016/S0090-4295(00)00649-X] [PMID: 10962318]
[72]
Sharma M, Satyavati GV, Raina MK, Eds. Medicinal plants of India. New Delhi: Indian Council of Medical Research 1976.
[73]
Roodenrys S, Booth D, Bulzomi S, Phipps A, Micallef C, Smoker J. Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology 2002; 27(2): 279-81.
[http://dx.doi.org/10.1016/S0893-133X(01)00419-5] [PMID: 12093601]
[74]
Russo A, Borrelli F. Bacopa monniera, a reputed nootropic plant: An overview. Phytomedicine 2005; 12(4): 305-17.
[http://dx.doi.org/10.1016/j.phymed.2003.12.008] [PMID: 15898709]
[75]
Chaudhari KS, Tiwari NR, Tiwari RR, Sharma RS. Neurocognitive Effect of Nootropic Drug Brahmi (Bacopa monnieri) in Alzheimer’s Disease. Ann Neurosci 2017; 24(2): 111-22.
[http://dx.doi.org/10.1159/000475900] [PMID: 28588366]
[76]
Charles PD, Ambigapathy G, Geraldine P, Akbarsha MA, Rajan KE. Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: Implications in memory formation. J Ethnopharmacol 2011; 134(1): 55-61.
[http://dx.doi.org/10.1016/j.jep.2010.11.045] [PMID: 21129470]
[77]
Mathur D, Goyal K, Koul V, et al. The molecular links of re-emerging therapy: A review of evidence of brahmi (Bacopa monniera). Front Pharmacol 2016; 7.
[78]
Chowdhuri DK, Parmar D, Kakkar P, Shukla R, Seth PK, Srimal RC. Antistress effects of bacosides of Bacopa monnieri: Modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. Phytother Res 2002; 16(7): 639-45.
[http://dx.doi.org/10.1002/ptr.1023] [PMID: 12410544]
[79]
Hepatoprotective activity of Bacopa monniera on d-galactosamine induced hepatotoxicity in rats. Nat Prod Sci 2007; 13: 195-8.
[80]
Le XT, Pham HTN, Do PT, et al. Bacopa monnieri ameliorates memory deficits in olfactory bulbectomized mice: Possible involvement of glutamatergic and cholinergic systems. Neurochem Res 2013; 38(10): 2201-15.
[http://dx.doi.org/10.1007/s11064-013-1129-6] [PMID: 23949198]
[81]
Saraf MK, Prabhakar S, Anand A. Neuroprotective effect of Bacopa monniera on ischemia induced brain injury. Pharmacol Biochem Behav 2010; 97(2): 192-7.
[http://dx.doi.org/10.1016/j.pbb.2010.07.017] [PMID: 20678517]
[82]
Sara SJ. Noradrenergic-cholinergic interaction: Its possible role in memory dysfunction associated with senile dementia. Arch Gerontol Geriatr Suppl 1989; 1: 99-108.
[PMID: 2569317]
[83]
Kamkaew N, Scholfield CN, Ingkaninan K, et al. Bacopa monnieri and its constituents is hypotensive in anaesthetized rats and vasodilator in various artery types. J Ethnopharmacol 2011; 137(1): 790-5.
[http://dx.doi.org/10.1016/j.jep.2011.06.045] [PMID: 21762768]
[84]
Konar A, Gautam A, Thakur MK. Bacopa monniera (CDRI-08) Upregulates the expression of neuronal and glial plasticity markers in the brain of scopolamine induced amnesic mice. Evid Based Complement Alternat Med 2015; 2015: 1-9.
[http://dx.doi.org/10.1155/2015/837012] [PMID: 26413129]
[85]
Limpeanchob N, Jaipan S, Rattanakaruna S, Phrompittayarat W, Ingkaninan K. Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. J Ethnopharmacol 2008; 120(1): 112-7.
[http://dx.doi.org/10.1016/j.jep.2008.07.039] [PMID: 18755259]
[86]
Holcomb LA, Dhanasekaran M, Hitt AR, Young KA, Riggs M, Manyam BV. Bacopa monniera extract reduces amyloid levels in PSAPP mice. J Alzheimers Dis 2006; 9(3): 243-51.
[http://dx.doi.org/10.3233/JAD-2006-9303] [PMID: 16914834]
[87]
Saraf MK, Anand A, Prabhakar S. Scopolamine induced amnesia is reversed by Bacopa monniera through participation of kinase-CREB pathway. Neurochem Res 2010; 35(2): 279-87.
[http://dx.doi.org/10.1007/s11064-009-0051-4] [PMID: 19757037]
[88]
Kishore K, Singh M. Effect of bacosides, alcoholic extract of Bacopa monniera Linn. (brahmi), on experimental amnesia in mice. Indian J Exp Biol 2005; 43(7): 640-5.
[PMID: 16053272]
[89]
Kapoor R, Srivastava S, Kakkar P. Bacopa monnieri modulates antioxidant responses in brain and kidney of diabetic rats. Environ Toxicol Pharmacol 2009; 27(1): 62-9.
[http://dx.doi.org/10.1016/j.etap.2008.08.007] [PMID: 21783922]
[90]
Farooqui AA, Farooqui T, Madan A, Ong JHJ, Ong WY. Ayurvedic medicine for the treatment of dementia: Mechanistic aspects. Evid Based Complement Alternat Med 2018; 2018: 1-11.
[http://dx.doi.org/10.1155/2018/2481076] [PMID: 29861767]
[91]
Goyal M. Rasayana in perspective of the present scenario. Ayu 2018; 39(2): 63-4.
[http://dx.doi.org/10.4103/ayu.AYU_300_18] [PMID: 30783358]
[92]
Gupta M, Shaw B. A double-blind randomized clinical trial for evaluation of galactogogue activity of asparagus racemosus willd. Iran J Pharm Res 2011; 10(1): 167-72.
[PMID: 24363697]
[93]
Uddin MS, Al Mamun A, Kabir MT, et al. Nootropic and anti-Alzheimer’s actions of medicinal plants: Molecular insight into therapeutic potential to alleviate Alzheimer’s neuropathology. Mol Neurobiol 2019; 56(7): 4925-44.
[http://dx.doi.org/10.1007/s12035-018-1420-2] [PMID: 30414087]
[94]
Kashyap P, Muthusamy K, Niranjan M, Trikha S, Kumar S. Sarsasapogenin: A steroidal saponin from Asparagus racemosus as multi target directed ligand in Alzheimer’s disease. Steroids 2020; 153: 108529.
[http://dx.doi.org/10.1016/j.steroids.2019.108529] [PMID: 31672628]
[95]
Smita SS, Raj Sammi S, Laxman TS, Bhatta RS, Pandey R. Shatavarin IV elicits lifespan extension and alleviates Parkinsonism in Caenorhabditis elegans. Free Radic Res 2017; 51(11-12): 954-69.
[http://dx.doi.org/10.1080/10715762.2017.1395419] [PMID: 29069955]
[96]
Pahwa P, Goel RK. Asparagus adscendens root extract enhances cognition and protects against scopolamine induced amnesia: An in-silico and in-vivo studies. Chem Biol Interact 2016; 260: 208-18.
[http://dx.doi.org/10.1016/j.cbi.2016.10.007] [PMID: 27717698]
[97]
Ojha R, Sahu AN, Muruganandam AV, Singh GK, Krishnamurthy S. Asparagus recemosus enhances memory and protects against amnesia in rodent models. Brain Cogn 2010; 74(1): 1-9.
[http://dx.doi.org/10.1016/j.bandc.2010.05.009] [PMID: 20594636]
[98]
Bopana N, Saxena S. Asparagus racemosus-Ethnopharmacological evaluation and conservation needs. J Ethnopharmacol 2007; 110(1): 1-15.
[http://dx.doi.org/10.1016/j.jep.2007.01.001] [PMID: 17240097]
[99]
Singh GK, Garabadu D, Muruganandam AV, Joshi VK, Krishnamurthy S. Antidepressant activity of Asparagus racemosus in rodent models. Pharmacol Biochem Behav 2009; 91(3): 283-90.
[http://dx.doi.org/10.1016/j.pbb.2008.07.010] [PMID: 18692086]
[100]
Sharma P, Srivastava P, Seth A, Tripathi PN, Banerjee AG, Shrivastava SK. Comprehensive review of mechanisms of pathogenesis involved in Alzheimer’s disease and potential therapeutic strategies. Prog Neurobiol 2019; 174: 53-89.
[http://dx.doi.org/10.1016/j.pneurobio.2018.12.006] [PMID: 30599179]
[101]
Zheng H, Amit T, Bar-Am O, et al. From anti-parkinson’s drug rasagiline to novel multitarget iron chelators with acetylcholinesterase and monoamine oxidase inhibitory and neuroprotective properties for Alzheimer’s disease. In: Riederer P, Laux G, Mulsant B, Eds. NeuroPsychopharmacotherapy Springer, Cham. pp. 1-26.
[http://dx.doi.org/10.1007/978-3-319-56015-1_234-1]
[102]
Preenon B, Anuradha M, Ajit K. Ayur-informatics: Establishing an ayurvedic medication for Parkinsons disorder. Int J Adv Chem Engin Biol Sci 2017; 4(1): 27.
[http://dx.doi.org/10.15242/IJACEBS.EAP117202]
[103]
Sekine T, Fukasawa N, Murakoshi I, Ruangrungsi NA. 9,10-dihydrophenanthrene from Asparagus racemosus. Phytochemistry 1997; 44(4): 763-4.
[http://dx.doi.org/10.1016/S0031-9422(96)00579-1]
[104]
Banjari I, Marček T, Tomić S, Waisundara VY. Forestalling the epidemics of Parkinson’s disease through plant-based remedies. Front Nutr 2018; 5: 95.
[http://dx.doi.org/10.3389/fnut.2018.00095] [PMID: 30425989]
[105]
Sui Z, Qi C, Huang Y, et al. Aqueous extracts from asparagus stems prevent memory impairments in scopolamine-treated mice. Food Funct 2017; 8(4): 1460-7.
[http://dx.doi.org/10.1039/C7FO00028F] [PMID: 28275781]
[106]
Goel RK, Prabha T, Kumar MM, Dorababu M, Prakash Singh G. Teratogenicity of Asparagus racemosus Willd. root, a herbal medicine. Indian J Exp Biol 2006; 44(7): 570-3.
[PMID: 16872047]
[107]
Alok S, Jain SK, Verma A, Kumar M, Mahor A, Sabharwal M. Plant profile, phytochemistry and pharmacology of Asparagus racemosus (Shatavari): A review. Asian Pac J Trop Dis 2013; 3(3): 242-51.
[http://dx.doi.org/10.1016/S2222-1808(13)60049-3]
[108]
Hyldgaard M, Mygind T, Meyer RL. Essential oils in food preservation: Mode of action, synergies, and interactions with food matrix components. Front Microbiol 2012; 3: 12.
[http://dx.doi.org/10.3389/fmicb.2012.00012] [PMID: 22291693]
[109]
Dhingra D, Parle M, Kulkarni SK. Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid, and metrifonate in mice. J Med Food 2006; 9(2): 281-3.
[http://dx.doi.org/10.1089/jmf.2006.9.281] [PMID: 16822217]
[110]
Barceloux DG. Nutmeg (Myristica fragrans Houtt.). Dis Mon 2009; 55: 373-9.
[111]
Ghosh A, Ghosh T. Herbal drugs of abuse. Sys Rev Pharm 2010; 1(2): 141-5.
[112]
Ehrenpreis JE, DesLauriers C, Lank P, Armstrong PK, Leikin JB. Nutmeg poisonings: A retrospective review of 10 years experience from the Illinois Poison Center, 2001-2011. J Med Toxicol 2014; 10(2): 148-51.
[http://dx.doi.org/10.1007/s13181-013-0379-7] [PMID: 24452991]
[113]
Jissa G, Sai-Sailesh K, Mukkadan J. Oral administration of nutmeg on memory boosting and regaining in Wistar albino rats. Bali Medical Journal 2014; 3(1): 3-10.
[http://dx.doi.org/10.15562/bmj.v3i1.61]
[114]
Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T. Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus. Fitoterapia 2002; 73(6): 536-9.
[http://dx.doi.org/10.1016/S0367-326X(02)00168-5] [PMID: 12385884]
[115]
Shirish DA, Veena KS, Sanjay BK. Anticonvulsant activity of roots and rhizomes of Glycyrrhiza glabra. Indian J Pharmacol 2002; 34: 251.
[116]
Ambavade SD, Kasture VS, Kasture SB. Anxiolytic activity of Glycyrrhiza glabra linn. J Nat Rem 2001; 1: 130-4.
[117]
Ju HS, Li XJ, Zhao BL, Han ZW, Xin WJ. Effects of glycyrrhiza flavonoid on lipid peroxidation and active oxygen radicals. Yao Xue Xue Bao 1989; 24(11): 807-12.
[PMID: 2618676]
[118]
Yokota T, Nishio H, Kubota Y, Mizoguchi M. The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment Cell Res 1998; 11(6): 355-61.
[http://dx.doi.org/10.1111/j.1600-0749.1998.tb00494.x] [PMID: 9870547]
[119]
Chakravarthi K, Avadhani R. Beneficial effect of aqueous root extract of Glycyrrhiza glabra on learning and memory using different behavioral models: An experimental study. J Nat Sci Biol Med 2013; 4(2): 420-5.
[http://dx.doi.org/10.4103/0976-9668.117025] [PMID: 24082744]
[120]
Hasanein P. Glabridin as a major active isoflavan from Glycyrrhiza glabra (licorice) reverses learning and memory deficits in diabetic rats. Acta Physiol Hung 2011; 98(2): 221-30.
[http://dx.doi.org/10.1556/APhysiol.98.2011.2.14] [PMID: 21616781]
[121]
DeLegge MH, Smoke A. Neurodegeneration and inflammation. Nutr Clin Pract 2008; 23(1): 35-41.
[http://dx.doi.org/10.1177/011542650802300135] [PMID: 18203962]
[122]
Cho MJ, Kim JH, Park CH, et al. Comparison of the effect of three licorice varieties on cognitive improvement via an amelioration of neuroinflammation in lipopolysaccharide-induced mice. Nutr Res Pract 2018; 12(3): 191-8.
[http://dx.doi.org/10.4162/nrp.2018.12.3.191] [PMID: 29854324]
[123]
Omar HR, Komarova I, El-Ghonemi M, et al. Licorice abuse: Time to send a warning message. Ther Adv Endocrinol Metab 2012; 3(4): 125-38.
[http://dx.doi.org/10.1177/2042018812454322] [PMID: 23185686]
[124]
Amantea D, Nappi G, Bernardi G, Bagetta G, Corasaniti MT. Post-ischemic brain damage: Pathophysiology and role of inflammatory mediators. FEBS J 2009; 276(1): 13-26.
[http://dx.doi.org/10.1111/j.1742-4658.2008.06766.x] [PMID: 19087196]
[125]
Singh N, Bhalla M, De Jager P, Gilca M. An overview on ashwagandha: A Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med 2011; 8(S5): 208-13.
[http://dx.doi.org/10.4314/ajtcam.v8i5S.9] [PMID: 22754076]
[126]
Dar NJ, Hamid A, Ahmad M. Pharmacologic overview of Withania somnifera, the Indian Ginseng. Cell Mol Life Sci 2015; 72(23): 4445-60.
[http://dx.doi.org/10.1007/s00018-015-2012-1] [PMID: 26306935]
[127]
Chengappa KNR, Bowie CR, Schlicht PJ, Fleet D, Brar JS, Jindal R. Randomized placebo-controlled adjunctive study of an extract of Withania somnifera for cognitive dysfunction in bipolar disorder. J Clin Psychiatry 2013; 74(11): 1076-83.
[http://dx.doi.org/10.4088/JCP.13m08413] [PMID: 24330893]
[128]
Jain S, Shukla SD, Sharma K, Bhatnagar M. Neuroprotective effects of Withania somnifera Dunn. in hippocampal sub-regions of female albino rat. Phytother Res 2001; 15(6): 544-8.
[http://dx.doi.org/10.1002/ptr.802] [PMID: 11536389]
[129]
Auddy B, Hazra J, Mitra A, Abedon B, Ghosal S. A Standardized Withania somnifera extract significantly reduces stress-related parameters in chronically stressed humans: a double-blind, randomized, placebo-controlled study. J Am Nutraceut Assoc 2020; 11: 50-6.
[130]
Baitharu I, Jain V, Deep SN, et al. Withanolide A prevents neurodegeneration by modulating hippocampal glutathione biosynthesis during hypoxia. PLoS One 2014; 9(10): e105311.
[http://dx.doi.org/10.1371/journal.pone.0105311] [PMID: 25310001]
[131]
Muruganandam AV, Kumar V, Bhattacharya SK. Effect of poly herbal formulation, EuMil, on chronic stress-induced homeostatic perturbations in rats. Indian J Exp Biol 2002; 40(10): 1151-60.
[PMID: 12693696]
[132]
Kumar S, Seal CJ, Howes MJR, Kite GC, Okello EJ. In vitro protective effects of Withania somnifera (L.) dunal root extract against hydrogen peroxide and β-amyloid(1-42)-induced cytotoxicity in differentiated PC12 cells. Phytother Res 2010; 24(10): 1567-74.
[http://dx.doi.org/10.1002/ptr.3261] [PMID: 20680931]
[133]
Bhattacharya SK, Kumar A, Ghosal S. Effects of glycowithanolides from Withania somnifera on an animal model of Alzheimer’s disease and perturbed central cholinergic markers of cognition in rats. Phytother Res 1995; 9(2): 110-3.
[http://dx.doi.org/10.1002/ptr.2650090206]
[134]
Singh M, Ramassamy C. In vitro screening of neuroprotective activity of Indian medicinal plant Withania somnifera. J Nutr Sci 2017; 6: e54.
[http://dx.doi.org/10.1017/jns.2017.48] [PMID: 29152258]
[135]
Uddin Q, Samiulla L, Singh VK, et al. Phytochemical and pharmacological profile of Withania somnifera dunal: A review. J Appl Pharm Sci 2012; 02(01): 170-5.
[136]
Sehgal N, Gupta A, Valli RK, et al. Withania somnifera reverses Alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proc Natl Acad Sci 2012; 109(9): 3510-5.
[http://dx.doi.org/10.1073/pnas.1112209109] [PMID: 22308347]
[137]
Sun GY, Li R, Cui J, et al. Withania somnifera and Its withanolides attenuate oxidative and inflammatory responses and up-regulate antioxidant responses in BV-2 microglial cells. Neuromolecular Med 2016; 18(3): 241-52.
[http://dx.doi.org/10.1007/s12017-016-8411-0] [PMID: 27209361]
[138]
Tohda C, Kuboyama T, Komatsu K. Dendrite extension by methanol extract of Ashwagandha (roots of Withania somnifera) in SK-N-SH cells. Neuroreport 2000; 11(9): 1981-5.
[http://dx.doi.org/10.1097/00001756-200006260-00035] [PMID: 10884056]
[139]
Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol 2005; 144(7): 961-71.
[http://dx.doi.org/10.1038/sj.bjp.0706122] [PMID: 15711595]
[140]
Gregory J, Vengalasetti YV, Bredesen DE, Rao RV. Neuroprotective herbs for the management of Alzheimer’s disease. Biomolecules 2021; 11(4): 543.
[http://dx.doi.org/10.3390/biom11040543] [PMID: 33917843]
[141]
Jayaprakasam B, Padmanabhan K, Nair MG. Withanamides in Withania somnifera fruit protect PC-12 cells from β-amyloid responsible for Alzheimer’s disease. Phytother Res 2010; 24(6): 859-63.
[http://dx.doi.org/10.1002/ptr.3033] [PMID: 19957250]
[142]
Kumar S, Harris RJ, Seal CJ, Okello EJ. An aqueous extract of Withania somnifera root inhibits amyloid β fibril formation in vitro. Phytother Res 2012; 26(1): 113-7.
[http://dx.doi.org/10.1002/ptr.3512] [PMID: 21567509]
[143]
Kuboyama T, Tohda C, Zhao J, Nakamura N, Hattori M, Komatsu K. Axon- or dendrite-predominant outgrowth induced by constituents from Ashwagandha. Neuroreport 2002; 13(14): 1715-20.
[http://dx.doi.org/10.1097/00001756-200210070-00005] [PMID: 12395110]
[144]
Ahmed ME, Javed H, Khan MM, et al. Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment. Protoplasma 2013; 250(5): 1067-78.
[http://dx.doi.org/10.1007/s00709-013-0482-2] [PMID: 23340606]
[145]
Gupta M, Kaur G. Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation. BMC Complement Altern Med 2019; 19(1): 217.
[http://dx.doi.org/10.1186/s12906-019-2635-0] [PMID: 31416451]
[146]
Kuboyama T, Tohda C, Komatsu K. Withanoside IV and its active metabolite, sominone, attenuate Aβ(25-35)-induced neurodegeneration. Eur J Neurosci 2006; 23(6): 1417-26.
[http://dx.doi.org/10.1111/j.1460-9568.2006.04664.x] [PMID: 16553605]
[147]
Ashwagandha. LiverTox: clinical and research information on drug-induced Liver Injury. Bethesda (MD): national institute of diabetes and digestive and kidney diseases 2012. Available from: http://www.ncbi.nlm.nih.gov/books/NBK548536/ (Accessed on: 17 June 2022).
[148]
Dar NJ, Muzamil A. Neurodegenerative diseases and Withania somnifera (L.): An update. J Ethnopharmacol 2020; 256: 112769.
[http://dx.doi.org/10.1016/j.jep.2020.112769] [PMID: 32240781]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy